In recent years, new, automated methods for the systematic preparation of new compounds, so-called “combinatorial techniques” have been developed. A wide variety of methodologies, tools and techniques wear the label of combinatorial methods. Generally these methods seek to accelerate the discovery of new materials and the application of new and known materials to new uses by increasing the number and rapidity of material tests though reductions in the size of material samples. A particular type of combinatorial methods focuses on the creation and/or analysis of arrays of materials at discrete locations on a substrate of some type. The substrates often comprise a base having regions defines by depressions, wells, walls of other structural means to separate the regions and keep the different materials in the arrays isolated for synthesis and analysis.
The size of the materials samples in the regions are of necessity kept small to achieve the objective of such arrays in the combinatorial methodology. Accordingly the diameter of the regions seldom exceeds 15 mm and usually presents regions of much smaller size. The small size of these regions can pose contamination problems. Contamination whether detected or undetected can interfere with the usefulness of such arrays by corrupting the data obtained from the material samples thereby leading to false conclusions that waste time and resources. Consequently reuse of a substrate such as a base that receives material directly on its surface requires thorough cleaning and/or treatment to avoid the presence of any contaminants from previous experiments. Since the regions are by definition small, intensive and thorough cleaning of the small areas can present a challenge. Moreover the composition of the substrate or base may exacerbate the problems. The use of easily machinable or formable materials facilitates the manufacture of the small structures on the surface of the base that define the vast number of small regions needed for such arrays. However easily machinable and formable materials are typically less susceptible to the harsh conditions needed to get the contaminants out of the small regions.
It is already known to synthesize a multitude of material samples in arrays of small vessels. For example, it is known to produce various metal oxides in small vessels having the form of individual crucibles retained by a base. The use of individual vessels allows their disposal or intensive cleaning once all experimental steps with the material contained therein are concluded. However, many of the synthesis operations, treatments steps and analysis of a material may require movement of the arrays. So on one hand the vessels must remain fixed in the base throughout such procedures that may in addition to movement between pieces of equipment require shaking stirring or agitation in the equipment. But at the same time the vessel must not become so fixed in the base or substrate that they are not readily removed for disposal. Fitting vessels into a base with a tight tolerance may prevent their removal after completion of the experiment. Moreover, certain treatment steps may create minor distortion of the vessels or the base that binds them together by the completion of the experiment.
Such conditions occur in the synthesis of many materials. One example of such materials, zeolites, are prepared by so-called hydrothermal synthesis at temperatures ranging from 100° C. to 200° C. requiring crystallization times of one hour or more. For syntheses being carried out at temperatures that are higher than the boiling point of the solvent, it is necessary to use pressure vessels, and these have to be suitable for the temperature and pressure used during the operation. This further requires the sealing of the vessels in a manner that prevents contamination between the materials undergoing synthesis.
Zeolite syntheses are usually performed in strongly alkaline media, often at pH>14, and the reaction mixture will often contain toxic chemicals such as, e.g., fluoride. Conventionally, syntheses that may be performed at temperatures lower than 110° C. are carried out in polymer bottles, often Teflon™ (tetrafluoroethylene), while reactions at higher temperatures require steel autoclaves, perhaps lined with Teflon™. Having a cost effective combinatorial method for such syntheses is quite useful since the price of an autoclave of this type with the required safety details is typically of the order of about 1,000 United States dollars or higher. Furthermore, such an autoclave will weigh from 1 kilogram and upwards, and all of these elements represent limitations regarding the number of syntheses that may be performed in most laboratories in the course of one year.
Zeolite synthesis is often carried out by keeping the synthesis mixture at around 100° C. for at least 6 h. At these moderate temperatures sealed chambers are necessary in order to avoid drying out of the synthesis mixture. U.S. Pat. No. 3,130,007 A exemplifies conventional zeolite synthesis. Common to all the synthesis procedures mentioned and for all other known synthesis procedures for the preparation of zeolites on a laboratory scale with the purpose of discovering new zeolites or to optimize existing zeolites is that these are performed in a cumbersome and expensive manner by having to separately prepare each reaction mixture, which typically consists of 4-7 reagents, and by adding the reagents one by one. In many other examples the synthesis of zeolites and other molecular sieves needs temperatures well above 100° C., so that steel pressure vessels or the like are required.
New, combinatorial techniques which may be used for liquid phase synthesis at temperatures above approximately 100° C. have been disclosed in WO 02/07873 that provides the synthesis to be performed in a hermetically sealed vessel at elevated pressures. There is, e.g., a known design called “multiblock”, see Krchnak, V.; Vagner, J. Peptide Res. 1990, 3,182, consisting of i) a Teflon™ block holding 42 reactors, polypropylene syringes equipped with polymer filters, ii) a vacuum adapter connecting each reactor to a vacuum line (not described in detail) which enables rapid washing in an apparatus for continuous flow, iii) two Teflon™ plates with 42 stoppers to which the Teflon™ block is fastened during use, and iv) a glass cover used during homogenization. The problem with this design is that the reactors which are made of glass and which do not have protected sidewalls may be used only at low pressures and not in strongly alkaline solutions.
Until recently there has been no available literature describing methods or equipment for using arrays that might be used for practical work to sufficiently retain vessels in the array to perform combinatorial experimentation while providing facile withdrawal of the vessels for replacement in the substrate or base. Zeolite synthesis can be particularly problematic inasmuch as such syntheses almost without exception require hydrothermal treatment of a solution or gel with a relatively high content of water and often high contents of organic compounds in a closed chamber under elevated temperatures and high pressure.
WO 98/36826 discloses a system for screening of synthesis conditions for the preparation of zeolites and other non-carbon materials requiring hydrothermal conditions in the temperature range of 100° C. to 250° C. Some of the parameters that have been made more cost efficient with the multiautoclave of WO 98/36826 include: reduced size of the separate reaction chambers and increased number of reaction chambers; reduced use of reactants; automated addition of reactants, for instance by a pipetting machine which makes quick and exact addition of all liquid reactants possible; and devices allowing automated analysis with X-ray diffraction and automatic identification of known crystalline phases. WO 98/36826 has also disclosed automated equipment for larger synthesis series and preparation formulations based on mixtures of different liquids/solutions with varying reactant ratios.
The WO 98/36826 invention is a pressure and temperature reactor vessel comprising a central block having a multitude of perforations. The perforations are through-going perforations, cavities or other form of holes permanently closed at one end. A cover engages the central block to seal the open ends of the perforations and form a multitude of chambers. A sealing means, operatively associated with the cover together form a pressure tight seal when a locking means holds cover in engagement with the sealing means to make reaction chambers pressure tight. Applications for the WO 98/36826 invention may, in addition to zeolite synthesis, be in any field of activities within research and development connected to products where at least one production step comprises the mixing of different liquids, e.g., in the fields of organic and inorganic syntheses, paint production, formulation of fuels, food industry, etc., and, furthermore, applications within clinical testing, dissolution and digestion of samples with acid etc. where a liquid reactant is added to a liquid or solid, or a solid is added to a liquid. The invention of WO/9836826 is most useful where open vessels cannot be used, and where it is required to operate at temperatures which will cause elevated pressures in the liquid part of the mixture.
The present invention is an advancement in the art as compared to WO/9836826 in that a set of vessels are removably secured within associated bores defined by a base. The vessels are constructed of material that is inert in the reactions or treatments conducted within a synthesis zone including a pressure and temperature conditions as may occur when using and substrate or base in any form from simple plate to a multi autoclave. The vessels, being each a single unit, line the interior of the bores, both the interior walls and one end. The vessels allow for a simple means of extracting material from the multiautoclave and can then be replaced with fresh vessels to minimize cross contamination between runs using the vessels. Optionally, the vessels may be used in the weighing of reagents such as powders and liquids for increased accuracy. Others have employed a liner in specific single vessel units such as U.S. Pat. No. 4,554,136 A where a fluoropolymer lining is used to inhibit acid corrosion of the walls of the pressure vessel, U.S. Pat. No. 3,048,481 A which discloses a refractory lining used within a synthesis gas generator, and U.S. Pat. No. 3,396,865 A which teaches a synthesis pressure vessel having a thermally conductive pressure shell and a chemically resistant thermally insulating lining within the shell made of a dense refractory concrete. The present invention, however, is unique in its use of a set of vessels to facilitate solid product removal and minimize cross contamination between runs using the array of vessels.